Exploratory Evaluation of the BiP Inhibitor BPR001-615 in Primary Cells and the Diagnostic Value of Circulating BiP in Colorectal Adenocarcinomas

Exploratory Evaluation of the BiP Inhibitor BPR001-615 in Primary Cells and the Diagnostic Value of Circulating BiP in Colorectal Adenocarcinomas

Colorectal cancer is one of the most common cancers worldwide. Although surgery and drug treatments have improved, some colorectal cancers may continue to grow or become resistant to treatment. Researchers are therefore looking for new biological targets that could help develop future therapies. BiP, also known as GRP78, is a protein normally present inside cells. It helps cells manage stress and maintain normal protein function. Cancer cells are often exposed to stressful conditions, such as low oxygen levels and limited nutrients. To survive in this environment, they may produce increased amounts of BiP. High BiP activity may help cancer cells avoid cell death, continue to grow, and become more resistant to treatment. BPR001-615 is an experimental compound developed to block the activity of BiP. The main hypothesis of the COLBiP study is that inhibition of BiP by BPR001-615 will reduce the viability and growth of human colorectal cancer cells in a dose-dependent manner. The compound will only be tested in the laboratory on tumor cells obtained during surgery. It will not be administered to participants, and the results of the laboratory tests will not be used to guide their treatment. COLBiP is a prospective, single-center, exploratory pilot study conducted at Nice University Hospital. The study will include 15 adult patients undergoing planned surgical removal of a confirmed colorectal adenocarcinoma. During the participant's usual hospital care, a 5 mL blood sample will be collected, preferably at the same time as routine blood sampling or placement of an intravenous line. After the tumor has been surgically removed, a small fresh tissue fragment will be collected from the surgical specimen. This sampling will not interfere with the tissue required for routine diagnosis, which will remain the priority. The tumor fragment will be transported to the C3M laboratory, where researchers will isolate the tumor cells and grow them in primary cell culture. These cells will then be exposed to increasing concentrations of BPR001-615. The effect of the compound will be evaluated by measuring cell viability and growth using two complementary laboratory methods: the WST-1 assay and cell counting with trypan blue exclusion. The researchers will establish a dose-response curve and, when possible, estimate the concentration of BPR001-615 required to reduce cell viability by 50%. In parallel, the amount of circulating BiP in the blood will be measured using an ELISA laboratory test. BiP expression within the tumor tissue will also be evaluated using immunohistochemistry. The study will explore whether circulating BiP levels, tumor BiP expression, and the response of the tumor cells to BPR001-615 are associated with one another. Researchers will also examine whether BiP levels are associated with routinely collected tumor characteristics, including tumor stage and histological features. There is no expected direct medical benefit for participants, and participation will not change their usual diagnosis, surgery, or treatment. The procedures specific to the study use blood and tumor tissue collected during routine care, and the additional risk is expected to be minimal. This pilot study aims to provide early evidence about the activity of BPR001-615 in human colorectal cancer cells and to assess whether BiP could be useful as a biomarker in future studies of BiP-targeted treatments.

Inclusion Criteria:

• Age 18 years or older.
• Histologically confirmed colorectal adenocarcinoma.
• Planned surgical resection of the primary colorectal tumor at Nice University Hospital.

Exclusion Criteria:

• Digestive tumor other than an adenocarcinoma, including a neuroendocrine tumor, lymphoma, gastrointestinal stromal tumor, or metastasis from another primary cancer.
• Intraoperative or pathological findings showing a diagnosis other than colorectal adenocarcinoma.